Flenniken is widely recognized as an influential figure in the integration of feminist concerns into underground comics. Her best-known creation is the comic strip Trots and Bonnie, a light-hearted satire of the adult world seen through the eyes of a precocious girl and her talking dog, illustrated in the vein of early comic strip artists like Clare Briggs and H. T. Webster.

Flenniken's Trots and Bonnie appeared from 1972 to 1990.

Flenniken was an editor of National Lampoon from 1979 to 1981, recruited many of the magazine's best-known cartoonists during that time, and co-wrote the screenplay of National Lampoon Goes to the Movies.